Cancer-supporting nitrites - an all-too-familiar story

Research from China suggests that even low levels of nitrites in drinking water can cause cancer. Why is the West ignoring the evidence? asks Oliver Tickell

The possibility of a link between nitrite in drinking water and cancer was first noted in 1970. To this day the view of the western ‘scientific establishment’ remains that the effects of nitrite – and the related substance nitrate – are well understood and there’s not much for us to worry about, though it is a good idea to eat less bacon and other preserved meats.

But Chinese scientists are reaching a very different view: that nitrite in drinking water is closely linked with cancer incidence and mortality. Indeed, nitrite pollution may be responsible for up to half of all cancer deaths in developed countries – even when nitrite and nitrate levels are within legal limits.

Nitrite is a common pollutant of rivers, streams, lakes and water supplies. It is also widely used as a meat preservative, both to prevent botulism and to give the meat an attractive dark red colour. In high doses it induces a state of anoxia in the blood known as ‘blue-baby syndrome’ or methemoglobinemia – a potentially fatal but mercifully rare condition. Nitrite in high doses is also linked with cancer as it can make carcinogenic nitrosamine and N-nitroso compounds. For this reason regulators have tried to reduce nitrite levels in food, and make sure it is used with ascorbic acid (vitamin C), which inhibits the formation of the carcinogens.

Nitrite and nitrate are readily interchangeable through reduction (of nitrate to nitrite) and oxidation (of nitrite to nitrate). Reducing conditions in the gut, for example, can cause nitrate to convert to nitrite, while exposure to oxygen does the reverse. Levels of both are regulated in drinking water. In the EU, drinking water may contain up to 0.5mg of nitrite per litre, and 50mg/l of nitrate. In the US, the limits are 1mg/l of nitrite and 10mg/l of nitrate. At first sight these levels seem fairly low, and after all we eat nitrate every day in ‘healthy’ fresh fruit and vegetables – so just how much is there to worry about?

In 2003, Xu Zhixiang published a summary of his research in his monograph Chemical Fertilizers, Pollution and Esophageal Cancer. Based upon his evidence, China may be divided into three zones: those of ‘low’ cancer mortality (less than 30 cases per 100,000); those of ‘high’ cancer mortality (more than 80 per 100,000) and those of ‘average’ cancer mortality in between those extremes. It turns out that the three cancer mortality areas correspond closely with areas of high, low and average levels of nitrite in drinking water.

This rings alarm bells, but is not in itself conclusive. As China has industrialised, many types of pollution have increased; nitrogen pollution may be a proxy for some other pollutant that is the real cause of the cancer surge. Further evidence comes from Linzhou County, Henan Province, in north China, however, whose boundaries encompass an area of about 2,000km² of dry, hilly country with a rapidly industrialising city at its core, and a population of about a million. The city has attracted attention due to its exceptionally high rate of oesophageal cancer, as described by Kenneth Hsu, director of the Centre for Environment and Health Engineering, Henan University, and colleagues, in a 2008 paper, Nitrite in Drinking Water and Cancer.

In 1964, the Hongqi Canal was linked to the polluted Zhuozhang River, and began to supply most of Linzhou’s drinking water. Soon after, cancer mortality soared; cases of oesophageal cancer more than doubled from 83 per 100,000 in the years 1959-1963 to 171 per 100,000 in 1972-1976. In 1970, cancer specialists from Beijing went to Linzhou to investigate the problem. Although nitrite levels were not high by western standards, in the range of 0.1 to 1.0mg/l, they recommended switching the water supply to low-nitrite sources.

So deep groundwater sources with less than 0.01mg/l of nitrite were developed, oxygen-poor water storage tanks that caused the reduction of nitrate to nitrite were decommissioned and oxygenated tap water was introduced. Oesophageal cancer mortality duly declined, reaching 86 per 100,000 in 1996-2000 – roughly back to the pre-1964 level. There were exceptions: the two Linzhou townships that continued to get their drinking water from the Hongqi Canal, where cancer mortality remained high, and three townships whose drinking water came from the Qi River, where cancer mortality remained at the same relatively low incidence. Similar experiences accumulated in other parts of China.

Thanks to the increasingly convincing evidence of the contribution of nitrite to cancer mortality, China now has some of the world’s most stringent laws on nitrite pollution. In 2005, the government reduced the maximum level of nitrite (as nitrogen) in bottled water from 0.005 to 0.002mg/l, one-500th of the level allowed in drinking water in the USA, and set a limit of 0.02mg/l of nitrite for groundwater recharge – yet still failed to set any maximum for nitrite in piped drinking water for fear of depriving many cities of their water supply.

The broad-scale epidemiological findings on nitrite and cancer in China have been complemented by laboratory experiments in Russia, Japan and Taiwan. A synthesis of the experimental results carried out by Hsu and his colleague Huangpo Chaoshen in 2008 suggests that nitrite is not directly carcinogenic – that is, it does not convert healthy cells into cancer cells – but that it does stimulate the growth of cancer cells. The degree of stimulation depends upon various factors, including the concentration of nitrite and the age and type of cancer cell. And cancer cell growth stimulus operates at the low concentrations of nitrite that apply to drinking water in the EU and the USA.

A possible explanation is that cancer cells use a different respiration mechanism to healthy cells. Instead of using mitochondria to produce energy from glucose through oxidative phosphorylation, cancer cells use glycolosis, a less-efficient energy pathway but one that can proceed in anaerobic conditions – as discovered in 1930 by the German biochemist Otto Warburg, winner of a Nobel Prize in 1931. This ‘Warburg effect’, largely ignored at the time, is now attracting interest once again as the glycolysing metabolism of cancer cells may be a key element of the ‘switch’ of a normal cell to a cancer cell.

Hsu concludes that nitrite may boost cancer cells’ respiration, helping them produce energy and grow, but thinks there must be more to it than that. For example, low levels of nitrite may act as a growth signal to cancer cells. He also wonders why nitrite in drinking water seems to be more potent than nitrite in food. It may be, for example, that a continuous low level of nitrite sends a stronger cancer-growth signal than high short-term levels fluctuating from a very low base.

Hsu is trying to disseminate to the western world the results of China’s experience of nitrite and cancer, but this is not proving easy. Much of the original research is available only in Chinese, and Hsu has encountered a reluctance in the West to revisit the nitrite and cancer question. Papers he has submitted to Nature and the Proceedings of the US National Academy of Sciences have been rejected, for example – in the latter case because there was insufficient ‘experimental evidence to support the hypothesis that nitrite can promote/sustain tumourigenesis’.

Hsu insists that there is plenty of evidence, but more importantly, he argues: ‘the point is to inform the public of the very well established statistical studies linking cancer death to nitrite pollution. The facts are undeniable and the most effective weapon in the “war against cancer” is to switch the source of drinking water. Cut nitrite to below 0.01mg/l in the UK and you could halve the cancer mortality of 165,000 people per year”, he says. Meanwhile in Europe, the USA and elsewhere, hundreds of millions of people are exposed to increased cancer risk.

Oliver Tickell is a writer and campaigner on health and environmental issues